漆黄素与β-环糊精衍生物的包合行为及性能研究  

Study on inclusion behavior and properties of fisetin withβ-cyclodextrin derivatives

作　　者：李燕华 王淑慧 李俊鹏 李文琳 左川 赵芳 LI Yan-hua;WANG Shu-hui;LI Jun-peng;LI Wen-lin;ZUO Chuan;ZHAO Fang(State Key Laboratory of Advanced Technologies for Comprehensive Utilization of Platinum Metals,Sino-Platinum Metals Co.,Ltd.,Kunming 650500,China;School of Chemistry and Environment,Yunnan Minzu University,Kunming 650106,China;Eryuan County Inspection and Testing Institute,Dali 671200,China)

机构地区：[1]贵研铂业股份有限公司稀贵金属综合利用新技术国家重点实验室,云南昆明650156 [2]云南民族大学化学与环境学院,云南昆明650500 [3]洱源县检验检测院,云南大理671200

出　　处：《中草药》2021年第16期4797-4810,共14页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(U1602271);云南省科技计划项目(2018ZE001);云南省科技计划项目(202002AB080001)。

摘　　要：目的制备漆黄素(fisetin,FIT)与β-环糊精衍生物的包合物,并对其包合行为和包合物的水溶性、稳定性进行研究。方法通过超声法制备了漆黄素与2-羟丙基-β-环糊精[(2-hydroxypropyl)-β-cyclodextrin,HP-β-CD]、2,6-二甲基-β-环糊精[(2,6-di-O-methyl)-β-cyclodextrin,DM-β-CD]和磺丁基醚-β-环糊精(sulfobutyl ether-β-cyclodextrin,SBE-β-CD)的包合物;采用核磁共振氢谱(1H-NMR和2D-NMR)、X射线粉末衍射(X-ray powder diffraction,XRD)、差示扫描量热法(differential scanning calorimetry,DSC)、扫描电子显微镜(scanning electron microscope,SEM)、紫外-可见光谱法(ultraviolet-visible spectrometry,UV)、Job曲线法对包合物进行表征;测定了包合物的水溶性,在模拟人体胃液和肠液环境下进行了稳定性的测试。结果核磁共振(1H-NMR和2D-NMR)分析表明,漆黄素从小口端进入HP-β-CD空腔,从大口端进入DM-β-CD和SBE-β-CD空腔。漆黄素与HP-β-CD、DM-β-CD和SBE-β-CD形成包合物后,其溶解度从0.05 mg/mL分别提高到了3.45、3.70、4.60 mg/mL。结论漆黄素与β-环糊精衍生物形成包合物后,其溶解度、热稳定性及生物环境稳定性得到明显提高。Objective To prepare fisetin(FIT)andβ-cyclodextrin(β-CD)derivatives inclusion complexes[hydroxypropyl-β-cyclodextrin(HP-β-CD),dimethyl-β-cyclodextrin(DM-β-CD),sulfobutyl ether-β-cyclodextrin(SBE-β-CD)]and explore their inclusion behavior and the water solubility and stability of inclusion complexes.Methods The inclusion complexes of FIT with HP-β-CD,DM-β-CD and SBE-β-CD were prepared by ultrasonic method.Optimize the best inclusion process with drug loading as an index.Inclusion complexes was characterized by 1 H-NMR and 2 D-NMR,X-ray powder diffraction(XRD),differential scanning calorimetry(DSC),scanning electron microscope(SEM),ultraviolet-visible spectrometry(UV-Vis),and Job curve methods;The water solubility of the inclusion complexes was measured and the stability test was conducted in the simulated human gastric juice and intestinal fluid environment.Results Nuclear magnetic resonance(1 H-NMR and 2 D-NMR)analysis showed that FIT entered the HP-β-CD cavity from the small mouth end,and entered the DM-β-CD and SBE-β-CD cavity from the big mouth end.The solubility of FIT was increased from 0.05 mg/mL to 3.45,3.70,4.60 mg/mL for HP-β-CD,DM-β-CD and SBE-β-CD,respectively.Conclusion The solubility,thermal stability and biological environment stability had been significantly improved after the formation of inclusion complex.

关 键 词：漆黄素 Β-环糊精 包合物 水溶性 稳定性 溶解度 

分 类 号：R283.6[医药卫生—中药学]